Management of hepatitis B virus prophylaxis in patients treated with disease-modifying therapies for multiple sclerosis: a multicentric Italian retrospective study

Abstract

Background Patients with multiple sclerosis (MS) often receive disease-modifying therapies (DMTs) that can expose them to reactivation of potential occult hepatitis B virus (HBV) infection (pOBI). We aimed to evaluate the MS Centers behavior regarding HBV screening and prophylaxis in a large cohort of MS patients receiving anti-CD20 or cladribine. Methods Retrospective, multicentric study recruiting Italian MS patients treated with rituximab, ocrelizumab and cladribine. Results We included 931 MS patients from 15 centers. All but 38 patients performed a complete HBV screening. Patients’ age > 50 years was significantly associated with no history of vaccination and HBsAb titres < 100 mIU at baseline (p < 0.001). No significant correlation was found between post-vaccination HBsAb titres and type of treatment (p = 0.5), pre-or post-therapy vaccination (p = 0.2) and number of previous DMTs (p = 0.2). Among pOBI patients (n = 53), 21 received antiviral prophylaxis, while only 13 had HBV DNA monitoring and 19 patients neither monitored HBV DNA nor received prophylaxis. Conclusions Baseline HBV screening in patients receiving anti-CD20 and cladribine is a consolidated practice. Nonetheless, HBV vaccination coverage is still lacking in such population and age is a significant factor associated with low HBV protection. Rituximab, ocrelizumab and cladribine did not impair HBV vaccine response. Almost 35% of pOBI patients fail to receive HBVr prevention. Management of HBV prophylaxis could be improved in MS patients and further prospective studies are needed to assess the effectiveness of prophylactic strategies in such patients.

Hepatitis B reactivation is a rare event among patients with resolved infection undergoing anti-CD20 antibodies in monotherapy without antiviral prophylaxis: results from the HEBEM study

“…Our results are especially relevant in view of the low rate of screening for HBVr in patients with MS undergoing rituximab-containing regimens. A recently published multicentre study including 53 anti-HBc-positive subjects showed that 21 received antiviral prophylaxis, and only 13 had HBV DNA monitoring during therapy for assessment of HBVr [ 5 ].…”

Overlooked complication of Cushing's syndrome: Reactivation of hepatitis B

“…HBV reactivation has been found in patients undergoing corticosteroid therapy in a number of studies 16,18,19 . In addition, there are studies in the literature investigating the risk of HBV reactivation in many different diseases that cause immunosuppression 20–23 . However, as far as we know there has been no research on HBV reactivation in CS, an immunosuppressive disease, and only case reports have been published.…”

“…16,18,19 In addition, there are studies in the literature investigating the risk of HBV reactivation in many different diseases that cause immunosuppression. [20][21][22][23] However, as far as we know there has been no research on HBV reactivation in CS, an immunosuppressive disease, and only case reports have been published. Since CS is an uncommon condition and HBV infection is not routinely screened for in the community, the frequency of HBV infection among this patient population is unknown.…”

Evaluation of BAFF, APRIL and CD40L in Ocrelizumab-Treated pwMS and Infectious Risk

“…However, B cells have been linked to MS and its progression as well as T cells [ 8 ], and the second-generation anti-CD20 recombinant humanized monoclonal antibody (mAb) ocrelizumab has been approved for the treatment of both relapsing–remitting MS (RRMS) and primary progressing MS (PPMS) [ 7 , 9 , 10 , 11 ]. It selectively induces B cell depletion, resulting in an immunosuppressive effect [ 12 , 13 , 14 , 15 ]. Although ocrelizumab efficiently depletes B cells in blood, some B cells and CD20 negative plasma cells persist in lymphatic organs and the inflamed central nervous system (CNS).…”

“…Finally, despite its remarkable efficacy, ocrelizumab is associated with an increased risk of infection and reactivation [ 12 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. Considering the intense B cell depletion induced by ocrelizumab, the aim of this study was to investigate the alterations in B cell activation markers prior to and during ocrelizumab treatment and their relationship with the occurrence of infectious events.…”